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Multiparameter Spectral Representation of Noise-Induced Competence in Bacillus Subtilis
Nov.-Dec. 2012 (vol. 9 no. 6)
pp. 1709-1723
K. Sargsyan, Sandia Nat. Labs., Livermore, CA, USA
C. Safta, Sandia Nat. Labs., Livermore, CA, USA
B. Debusschere, Sandia Nat. Labs., Livermore, CA, USA
H. Najm, Sandia Nat. Labs., Livermore, CA, USA
In this work, the problem of representing a stochastic forward model output with respect to a large number of input parameters is considered. The methodology is applied to a stochastic reaction network of competence dynamics in Bacillus subtilis bacterium. In particular, the dependence of the competence state on rate constants of underlying reactions is investigated. We base our methodology on Polynomial Chaos (PC) spectral expansions that allow effective propagation of input parameter uncertainties to outputs of interest. Given a number of forward model training runs at sampled input parameter values, the PC modes are estimated using a Bayesian framework. As an outcome, these PC modes are described with posterior probability distributions. The resulting expansion can be regarded as an uncertain response function and can further be used as a computationally inexpensive surrogate instead of the original reaction model for subsequent analyses such as calibration or optimization studies. Furthermore, the methodology is enhanced with a classification-based mixture PC formulation that overcomes the difficulties associated with representing potentially nonsmooth input-output relationships. Finally, the global sensitivity analysis based on the multiparameter spectral representation of an observable of interest provides biological insight and reveals the most important reactions and their couplings for the competence dynamics.
Index Terms:
stochastic processes,belief networks,biological techniques,biology computing,chaos,microorganisms,optimisation,global sensitivity analysis,multiparameter spectral representation,noise-induced competence,stochastic forward model output,stochastic reaction network,Bacillus subtilis bacterium,polynomial chaos spectral expansion,Bayesian framework,PC mode,posterior probability distribution,reaction model,calibration,optimization,classification-based mixture PC formulation,Response surface methodology,Uncertainty,Stochastic processes,Computational modeling,Computational biology,Bioinformatics,probability and statistics,Approximation,spectral methods
K. Sargsyan, C. Safta, B. Debusschere, H. Najm, "Multiparameter Spectral Representation of Noise-Induced Competence in Bacillus Subtilis," IEEE/ACM Transactions on Computational Biology and Bioinformatics, vol. 9, no. 6, pp. 1709-1723, Nov.-Dec. 2012, doi:10.1109/TCBB.2012.107
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